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In this study, we describe a novel solid-state thin-film Ag/AgCl reference electrode (SSRE) that was coated with a protective layer of graphene oxide (GO). This layer was prepared by drop casting a solution of GO on the Ag/AgCl thin film. The potential differences exhibited by the SSRE were less than 2 mV for 26 days. The cyclic voltammograms of the SSRE were almost similar to those of a commercial reference electrode, while the diffusion coefficient of Fe(CN)63− as calculated from the cathodic peaks of the SSRE was 6.48 × 10−6 cm2/s. The SSRE was used in conjunction with a laboratory-made working electrode to determine its suitability for practical use. The average pH sensitivity of this combined sensor was 58.5 mV/pH in the acid-to-base direction; the correlation coefficient was greater than 0.99. In addition, an integrated pH sensor that included the SSRE was packaged in a secure digital (SD) card and tested. The average sensitivity of the chip was 56.8 mV/pH, with the correlation coefficient being greater than 0.99. In addition, a pH sensing test was also performed by using a laboratory-made potentiometer, which showed a sensitivity of 55.4 mV/pH, with the correlation coefficient being greater than 0.99.

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target. Different types of metabolic rewiring are reported to drive cancer development and as a potential therapeutic target. Here, the authors perform multi-omics analyses in a cohort of human normal and malignant thyroid samples and show association of mitochondrial one-carbon metabolism with undifferentiated thyroid cancer.

Lithium titanium oxide (LTO: Li₄Ti₅O₁₂) particles were produced via a continuous supercritical fluid process for use as anodes in lithium ion batteries. The synthesized LTO particles in supercritical water (scH₂O) or in supercritical methanol (scMeOH) generate nanoparticles of 10–30 nm sizes, and the modified LTO particles using oleylamine in scMeOH affects the inhibition of particle growth. The modified LTO particle was coated by the usage of supercritical carbon dioxide (scCO₂) and polyethylene glycol (PEG-400). The conformal coverage of the carbon layer on LTO particles with a thickness of 1.2 nm, and a uniform distribution of carbon on the entire surface of LTO particles are confirmed. The modified and carbon-coated LTO with a carbon content of 5.3 wt% exhibits a high discharge capacity of 175 mAh/g (which approaches the theoretical value of LTO) at 0.1 C and 83 mAh/g at 50 C. The carbon-coated LTO prepared using supercritical fluids delivered 160, 153, 123 mAh/g at 1 C and 60 °C, room temperature, and −25 °C, respectively.

Insulin regulates blood glucose levels by binding its receptor and stimulating downstream proteins through the insulin receptor substrate (IRS). Impaired insulin signalling leads to metabolic syndrome, but the regulation of this process is not well understood. Here, we describe a novel insulin signalling regulatory pathway involving TAZ. TAZ upregulates IRS1 and stimulates Akt- and Glut4-mediated glucose uptake in muscle cells. Muscle-specific TAZ-knockout mice shows significantly decreased Irs1 expression and insulin sensitivity. Furthermore, TAZ is required for Wnt signalling-induced Irs1 expression, as observed by decreased Irs1 expression and insulin sensitivity in muscle-specific APC- and TAZ-double-knockout mice. TAZ physically interacts with c-Jun and Tead4 to induce Irs1 transcription. Finally, statin administration decreases TAZ, IRS1 level and insulin sensitivity. However, in myoblasts, the statin-mediated decrease in insulin sensitivity is counteracted by the expression of a constitutively active TAZ mutant. These results suggest that TAZ is a novel insulin signalling activator that increases insulin sensitivity and couples Hippo/Wnt signalling and insulin sensitivity. Insulin resistance is associated with development of type 2 diabetes. Here the authors show that TAZ interacts with c-Jun and Tead4, inducing expression of the insulin receptor substrate 1 (IRS1) leading to increased glucose uptake in muscle, and that its activity is counteracted by statin administration.

This study evaluated the prognostic implications of post-percutaneous coronary intervention (PCI) neutrophil-to-lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI). A total of 309 patients with AMI who underwent cardiac magnetic resonance imaging (CMR) and a complete blood cell count within 24 hours before and after PCI were enrolled. Primary outcome was infarct size. Patients were assigned to high (n = 118) or low (n = 191) NLR groups according to the best cut-off value of 3.88. Infarct size (% of total left ventricular mass) was significantly higher in the high NLR group than in the low NLR group (24.1 ± 11.0 vs. 16.7 ± 9.1, p < 0.001). Post-PCI NLR ≥ 3.88 was associated with risk of a large-sized infarction (≥20%) (OR 2.91, 95% CI 1.73–4.88, p < 0.001). The risk of MACE was also significantly higher in the high NLR group than in the low NLR group (15.8% vs. 7.4%, HR 2.60, 95% CI 1.21–5.60, p = 0.015). Among patients with AMI who underwent PCI, high post-PCI NLR value was associated with higher risk of large-sized infarction as measured by CMR, as well as adverse clinical outcomes. Our findings suggest that post-PCI NLR is a useful tool for risk assessment in patients with AMI who undergo PCI.

AimsThis study evaluated the sex differences of sequential changes in coronary blood flows and microvascular function in patients with suspected angina but with no obstructed coronary arteries.MethodsA total of 202 consecutive patients who experienced chest pain but had no significant coronary artery stenosis and who underwent adenosine stress echocardiography were included in the study. Coronary blood flow (CBF) velocities were measured at 1, 2, and 3 min after adenosine infusion.ResultsThe mean age was 61 years, and 138 (68%) were women. Approximately 40% of patients had coronary microvascular dysfunction (CMD, coronary flow velocity reserve < 2.3), with women exhibiting higher CMD prevalence. The left ventricular (LV) mass index was similar between men and women, while women exhibited higher baseline rate pressure products (RPP). At baseline, coronary blood flow velocities were similar between the sexes. However, CBF velocities in women gradually increased during the examination; and in men, the increase was abrupt and steep during the early stages of examination (p = 0.015 for interaction between time and sex), even with similar RPP in stress. Coronary flow velocity reserve was steadily lower in women compared to men (1 min, 2.09 ± 0.86 vs 2.44 ± 0.87; 2 min, 2.39 ± 0.72 vs 2.63 ± 0.85; 3 min, 2.45 ± 0.70 vs 2.68 ± 0.73).ConclusionsIn patients with suspected angina but with no obstructed coronary arteries, CMD was especially prevalent among women. Women exhibited higher oxygen consumption, while exhibiting slower and gradual increases in CBF velocities. Conversely, men exhibited faster and steeper increases in CBF velocities even with similar RPP in stress.

The regeneration of bone defects caused by periodontal disease or trauma is an important goal. Porous hydroxyapatite (HA) is an osteoconductive graft material. However, the hydrophobic properties of HA can be a disadvantage in the initial healing process. HA can be coated with TiO2 to improve its hydrophilicity, and ultraviolet irradiation (UV) can further increase the hydrophilicity by photofunctionalization. This study was designed to evaluate the effect of 5% TiO2-coated HA on rabbit calvarial defects and compare it with that of photofunctionalization on new bone in the early stage. The following four study groups were established, negative control, HA, TiO2-coated HA, and TiO2-coated HA with UV. The animals were sacrificed and the defects were assessed by radiography as well as histologic and histomorphometric analyses. At 2 and 8 weeks postoperatively, the TiO2-coated HA with UV group and TiO2-coated HA group showed significantly higher percentages of new bone than the control group (p < 0.05). UV irradiation increased the extent of new bone formation, and there was a significant difference between the TiO2-coated HA group and TiO2-coated HA with UV group. The combination of TiO2/HA and UV irradiation in bone regeneration appears to induce a favorable response.

Endotracheal suctioning is an essential but labor-intensive procedure, with the risk of serious complications. A brand new automatic closed-suction device was developed to alleviate the workload of healthcare providers and minimize those complications. We evaluated the clinical efficacy and safety of the automatic suction system in mechanically ventilated patients with pneumonia. In this multicenter, randomized, non-inferiority, investigator-initiated trial, mechanically ventilated patients with pneumonia were randomized to the automatic device (intervention) or conventional manual suctioning (control). The primary efficacy outcome was the change in the modified clinical pulmonary infection score (CPIS) in 3 days. Secondary outcomes were the frequency of additional suctioning and the amount of secretion. Safety outcomes included adverse events or complications. A total of 54 participants, less than the pre-determined number of 102, were enrolled. There was no significant difference in the change in the CPIS over 72 h (−0.13 ± 1.58 in the intervention group, −0.58 ± 1.18 in the control group, p = 0.866), but the non-inferiority margin was not satisfied. There were no significant differences in the secondary outcomes and safety outcomes, with a tendency for more patients with improved tracheal mucosal injury in the intervention group. The novel automatic closed-suction system showed comparable efficacy and safety compared with conventional manual suctioning in mechanically ventilated patients with pneumonia.

Early identification of women at high risk for cardiovascular diseases (CVD), with subsequent monitoring, will allow for improved clinical outcomes and generally better quality of life. This study aimed to identify the associations between early menopause, abnormal diastolic function, and clinical outcomes. This retrospective study included 795 menopausal women from is a nationwide, multicenter, registry of patients with suspected angina visiting outpatient clinic. The patients into two groups: early and normal menopause (menopausal age ≤ 45 and > 45 years, respectively). If participants met > 50% of the diastolic function criteria, they were classified as having normal diastolic function. Multivariable-adjusted Cox models were used to test associations between menopausal age and clinical outcomes including the incidence of major adverse cardiovascular events (MACE), over a median follow-up period of 771 days. Early menopause was associated with increased waist circumference ( p  = 0.001), diabetes prevalence ( p  = 0.003), obstructive coronary artery disease ( p  = 0.005), abnormal diastolic function ( p  = 0.003) and greater incidences of MACE, acute coronary syndrome, and hospitalization for heart failure. In patients with abnormal diastolic function, early menopause increased MACE risk significantly, with no significant difference in normal diastolic function. These findings highlight early menopause and abnormal diastolic function as being potential risk markers in women for midlife CVD events.